Abstract

Background:Sleep complaints are common among patients with traumatic brain injury. Evaluation of this population is confounded by polypharmacy and comorbid disease, with few studies addressing combat-related injuries. The aim of this study was to assess the prevalence of sleep disorders among soldiers who sustained combat-related traumatic brain injury.

Methods:The study design was a retrospective review of soldiers returning from combat with mild to moderate traumatic brain injury. All underwent comprehensive sleep evaluations. We determined the prevalence of sleep complaints and disorders in this population and assessed demographics, mechanism of injury, medication use, comorbid psychiatric disease, and polysomnographic findings to identify variables that correlated with the development of specific sleep disorders.

Conclusions:Sleep disruption is common following traumatic brain injury, and the majority of patients develop a chronic sleep disorder. It appears that sleep disturbances may be influenced by the mechanism of injury in those with combat-related traumatic brain injury, with blunt injury potentially predicting the development of OSAS.

Approximately 1.7 million people sustain a traumatic brain injury (TBI) every year in the United States, with 1.1 to 1.4 million treated in EDs, 235,000 to 275,000 hospitalized and surviving to discharge, and 50,000 deaths.1,2 Mild TBI comprises the majority of cases (70%-90%).3,4 Estimates of long-term disability secondary to TBI are 1.1% of the US population (3.2 million people).1,5 Of those who survive hospitalization, 43.2% (124,626 of 288,009) experience long-term disability.6 TBI can lead to delayed neurocognitive, psychiatric, and behavioral disturbances7 and may be a risk factor for dementia.8 These sequelae have led to an increased awareness of the long-term negative impact of head injuries, particularly among athletes and US military service members.

Sleep disturbances following TBI encompass a broad array of subjective sleep complaints and objective sleep-wake disturbances and have been reported in up to 72.5% of patients.9‐17 The estimated prevalence of sleep-disordered breathing (SDB) in TBI has been reported to be between 23% and 36% of patients.11,17 Sleep disorders in this population are increased and include obstructive sleep apnea,10,11,17,18 insomnia,15,19 circadian rhythm sleep disturbances,20 posttraumatic hypersomnia,10,11,15,18,21 and narcolepsy.10,11,18 Sleep disturbances after TBI have been related to hypothalamic injury, with decreased production and neurotransmission of hypocretin (orexin) and histamine21‐23 as well as decreased endogenous production of melatonin.24

TBI has become the signature injury of Operation Enduring Freedom and Operation Iraqi Freedom. Identification of TBI has risen among deployed service members.25 Since 2000, there have been 178,876 documented cases of TBI among military service members, with 167,913 sustained in Afghanistan and Iraq.26 Among survivors, the majority (82% [137,328]) of injuries have been mild. However, both moderate (30,893) and severe (1,981) injuries have been identified.26 Most are the result of blast or blunt force trauma, but penetrating injuries have occurred in 3,175 individuals.26

Understanding the impact of TBI on sleep disorders in this population is challenging because the effects of medications, other injuries, and subsequent medical-psychiatric disorders may confound the clinical picture. Sleep disturbances have a negative impact on rehabilitation in patients with TBI,27 with worsened cognition (sustained attention and memory)28 and long-term functional outcomes.18 Despite the growing knowledge of the frequency of sleep disorders in this population and their adverse impact on outcomes, most studies are limited by sample size, and few address combat-related injuries. The aim of the present study was to determine the prevalence of sleep disturbances among patients with combat-related TBI and to determine which clinical variables were associated with subjective sleep complaints.

Materials and Methods

Study Design

We conducted a retrospective review of consecutive soldiers with combat-related TBI receiving care at our facility between April 2005 and January 2010. All patients were aged ≥ 18 years and had sustained a nonpenetrating TBI during deployments to Iraq and Afghanistan. We excluded those with sleep disorders that were diagnosed prior to their injury; otherwise, no records were excluded from the final analysis. This study was approved by the Institutional Review Board within the hospital’s Department of Clinical Investigation (Walter Reed Army Medical Center IRB Exempt Protocol #355213-1).

TBI was verified in each patient by a review of clinical notes from the hospital’s TBI screening program. Soldiers with suspected TBI were screened using the 3-Question Defense and Veterans Brain Injury Center TBI Screening Tool, also known as the Brief Traumatic Brain Injury Screen.29 The questions are directed at the type of injury and severity of symptoms. The screening tool has been previously validated in returning veterans from Afghanistan and Iraq.29,30 In the validation study,30 83% of soldiers evaluated with a follow-up interview self-reported symptoms consistent with mild TBI based on American Congress of Rehabilitation Medicine criteria.31 Mild TBI is defined as meeting at least one of the following criteria postinjury: any period of loss of consciousness; posttraumatic amnesia; alteration in mental status at the time of the accident; and focal neurologic deficits that may or may not be transient, with loss of consciousness not exceeding 30 min, an initial Glasgow Coma Scale score of 13 to 15 (30 min postinjury), and posttraumatic amnesia not . 24 h.31 The Brief Traumatic Brain Injury Screen questionnaire can be found at http://www.dvbic.org/images/pdfs/3-Question-Screening-Tool.aspx, and the Veterans Administration/Department of Defense diagnostic algorithm for mild TBI32 can be found at http://www.healthquality.va.gov/mtbi/concussion_mtbi_full_1_0.pdf. Patients with higher degrees of TBI severity (moderate and severe) were given a diagnosis based on clinical evaluation in the TBI clinic.

All patients identified with a TBI underwent a formal consultation with a board certified sleep medicine physician in the sleep medicine clinic at our hospital. Data were obtained from a closed electronic medical record and included the initial sleep consultation, follow-up evaluations, and polysomnographic testing. Clinical variables included age, sex, BMI, and subjective assessments of sleep quality and daytime somnolence. Subjective assessments of daytime somnolence were assessed using the Epworth Sleepiness Scale (ESS),33 a visual analog fatigue score, and directed questioning regarding subjective complaints of excessive daytime somnolence. Subjective assessments of sleep quality included average sleep latency, subjective sleep fragmentation (complaints of nocturnal awakening), and unrefreshing sleep. Severity of TBI, mechanism of injury (blast vs blunt trauma), and comorbid psychiatric conditions were recorded in each patient. All psychoactive medications at the time of the initial sleep evaluation were recorded.

Those patients with a clinical suspicion for SDB (habitual snoring, subjective sleep fragmentation, nonrestorative sleep, witnessed apneas, or daytime somnolence not better explained by another process), underwent level 1, attended, overnight polysomnography. Polysomnography was performed using a 16-channel montage (Sensormedics β Somnostar system; Sensormedics Corp) and consisted of continuous recordings of central and occipital EEGs, bilateral electrooculograms, submental and bilateral tibial electromyograms, and ECG. Nasal and oral airflow were measured using both thermocouple sensors and pressure transducer airflow monitoring devices. Tracheal sounds were monitored using an acoustic microphone. Thoracic and abdominal excursions were measured using inductance plethysmography. Continuous oxygen saturation was assessed using noninvasive pulse oximetry. Body positioning was verified by infrared video recording. Studies were scheduled to last between 6 and 8 h and were terminated following the final wakening. All polysomnograms were scored and interpreted by the study investigators in accordance with guidelines published by the American Academy of Sleep Medicine (AASM).34,35 No autoscoring techniques were used. Given the age of the cohort, we defined hypopneas using the alternate AASM scoring criteria of a ≥ 50% reduction in pressure transducer airflow associated with a ≥ 3% decrease in oxygen saturation as measured by pulse oximetry or an EEG arousal.34 Prior to 2007, hypopneas were scored in accordance with earlier published criteria.35 Polysomnographic data used in this analysis included total sleep time, sleep latency, sleep efficiency, total arousal index, periodic limb movements (PLMs), and the apnea-hypopnea index (AHI).

The presence of insomnia and obstructive sleep apnea syndrome (OSAS) was determined for each patient. We defined insomnia as a subjective sleep latency of ≥ 30 min during the majority of nights or subjective sleep fragmentation (nocturnal awakening) associated with daytime impairment not better explained by SDB, pain, or other more likely identifiable factors in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for the diagnosis of insomnia.36 The diagnosis of OSAS was based on an AHI ≥ 5 events/h plus clinical symptoms of excessive daytime somnolence and SDB in accordance with AASM criteria.37

End Points

The primary end point was the prevalence of sleep complaints, insomnia, and OSAS among soldiers with combat-related TBI. The association between the development of sleep disorders and mechanism of injury (blast vs blunt), medication use, and comorbid psychiatric illnesses served as a secondary end point.

Statistical Analysis

Data are presented as the mean ± SD. The υ2 analysis and Fisher exact test were used to compare categorical variables. P < .05 was assumed to represent statistical significance. Continuous variables were assessed for normality using histogram graphs prior to using the independent samples t test for comparisons. Levene test was used to assess for equal variances among continuous variables being compared. Variables were included in multivariate logistic regression analysis if they reached P ≤ .20 on univariate analysis. Data were analyzed using PASW Statistics 17 (SPSS Inc).

Results

The cohort comprised 116 patients, predominantly men (96.6%). The mean age was 31.1 ± 9.8 years, and the mean BMI was 27.8 ± 4.1 kg/m2 (Table 1). TBI severity was rated as mild in 84.5%, moderate in 8.6%, and severe in 6.0%. The mean time between injury and sleep evaluation was 16.1 ± 11.5 months. Sleep complaints were nearly universal (97.4%). Poor sleep quality was reported by 81.9%, and 54.3% of patients reported sleep fragmentation. The majority (85.2%) reported excessive daytime somnolence. Among the cohort, the mean visual analog fatigue score was 6.8 ± 2.1, and the mean ESS score was 9.8 ± 5.2, with 45.2% having an ESS score . 10.

Nocturnal polysomnography was performed in 79.3% of the patients (Table 2). Mean sleep latency was 28.1 ± 34.4 min. Sleep fragmentation was common, with a mean sleep efficiency of 86.3% ± 12.1% and mean total arousal index of 17.7 ± 11.5 events/h. The mean PLM index among the cohort was 13.3 ± 6.4, with 19.5% having a PLM index of . 10/h. OSAS was diagnosed in 34.5% of the entire cohort and in 43.5% of those who underwent polysomnography, with a mean AHI of 9.1 ± 13.2 events/h among all patients and 17.9 ± 16.0 among those with OSAS. Insomnia was diagnosed in 55.2% based on DSM-IV diagnostic criteria.

Comorbid psychiatric conditions were common among the cohort, with 90.5% having at least one diagnosed condition. More than one-half (56.9%) had posttraumatic stress disorder (PTSD), 85.3% had depression, and 41.4% had an anxiety disorder. The use of psychoactive medications was similarly common. At the time of the initial sleep evaluation, nearly the entire cohort (94.0%) was prescribed psychoactive medications, with a mean of 5.0 ± 3.4 psychoactive medications and 3.3 ± 1.7 classes of psychoactive agents per patient (Table 3).

All variables in Table 5 with P < .20 were entered into this model (age, excessive daytime sleepiness, fragmented sleep, poor sleep quality, PTSD, blast injury, blunt injury, narcotics). The variable fragmented sleep was excluded from this model because it was highly correlated with the variable poor sleep quality (Spearman correlation r ± 0.513). Blast injury was excluded from this model because it was highly correlated with blunt injury, which was to be expected because this is a dichotomous variable and every patient had one or the other type of injury. PTSD and on narcotics were excluded from this model after using backward, stepwise regression to assess model performance. See Table 1 legend for expansion of abbreviations.

We also performed a comparison of patients with TBI based on the presence or absence of insomnia (Table 7). There was a high proportion of patients who rated their sleep as poor in both groups, which, not surprisingly, was significantly higher in the insomnia group compared with the group without insomnia (98.4% vs 61.5%, respectively; P < .001). There was a trend toward a greater number of psychoactive medications, particularly narcotics, in patients with insomnia. On multivariate analysis, only narcotic use (OR, 3.07; 95% CI, 1.20-7.87; P ± .02) and subjective poor sleep quality were predictive for the presence of insomnia (Table 8). Although we found a higher rate of insomnia among those with blast injuries, mechanism of injury was not predictive of insomnia in multivariate analysis.

All variables in Table 7 with P ≤ .20 were entered into this model (poor sleep quality, No. [psychoactive medication] classes, No. [psychoactive] medications, and on narcotics). The variables No. psychoactive classes and No. psychoactive medications were highly correlated, so only the No. psychoactive medications was incorporated into the final model.

Discussion

Similar to prior reports, sleep disruption and daytime somnolence were nearly universal among the present cohort of patients with combat-related TBI. Insomnia was seen in nearly one-half of the cohort, and nearly one-third were given a diagnosis of OSAS. The results suggest that the mechanism of injury may have a significant impact on the development of specific sleep disorders.

Several prior reports have noted that the rates of sleep disorders following TBI are significantly greater than in the general population.9,12‐14,20,21,38,39 Among 10 randomly selected patients assessed by Castriotta et al,18 seven were found to have SDB, and three had posttraumatic narcolepsy or posttraumatic hypersomnia. In a retrospective study of 60 adults with TBI (40% mild severity, 20% moderate, 40% severe), Verma et al16 found that 50% reported hypersomnia, 25% had insomnia, and 25% developed a parasomnia, the majority of which had rapid eye movement behavior disorder. Similar to the present study, they reported clinically significant SDB in 30% of the patients. In a prospective study of 31 adult patients, sleep disturbances were reported in 68% following closed head injuries.38 The prevalence of sleep complaints was independent of age, injury severity, and Glasgow Coma Scale on admission.

Insomnia is exceedingly common following TBI and may be more frequently associated with milder injuries.9,12,13 Most studies do not clearly differentiate between those with an objectively defined insomnia syndrome and subjective complaints of poor sleep quality.39 Insomnia is estimated to develop in 30% to 65% of patients with TBI13,14,20,39 and can persist for up to 3 years postinjury.40 Ouellet et al39 evaluated 452 patients with TBI with a questionnaire focusing on sleep quality and fatigue. The authors defined insomnia syndrome according to the International Classification of Sleep Disorders and DSM-IV criteria.41,42 They found that 50.2% had insomnia symptoms and 29.4% met criteria for insomnia syndrome. The majority developed symptoms within days postinjury, and the authors hypothesized that insomnia represents an acute reaction to TBI.

Multiple studies and reviews have documented the comorbid association between insomnia and SDB, with additive negative impacts on sleep quality, worsened neurocognitive function,43 and increased anxiety and depression.44‐46 In addition, insomnia may worsen therapeutic adherence with CPAP therapy in patients with obstructive sleep apnea.47

Comorbid psychiatric illnesses are common in those with sleep disorders, and chronic sleep disruptions can lead to impaired mood and depression.48 Similarly, anxiety, depression, and PTSD frequently develop following TBI. In a study assessing risk factors for sleep disruptions following closed head injuries, Rao et al49 found that postinjury anxiety disorders were more predictive of sleep disturbances than pain, comorbid disease, or medication side effects. Similarly, Shekleton et al24 found that patients with TBI had significantly more anxiety, depression, and sleep-wake disturbances than control patients. We found high rates of PTSD and depression among the present cohort. These may be influenced by the pattern of injury, as we observed that anxiety disorders and insomnia were more common in those with blast trauma.

The majority of the present cohort was using psychoactive medications long term to treat neuropathic pain, depression, anxiety, PTSD, or insomnia. Because the majority of the study population was using psychoactive agents, our ability to evaluate the impact of medication use or a particular class of medications on sleep disorders was limited. The finding that narcotic use predicted the presence of insomnia may be influenced by multiple factors. Studies primarily assessing insomnia in methadone users have found that insomnia is highly prevalent and likely affected by concurrent use of nicotine and alcohol in addition to psychiatric disease and unstable life circumstances.50,51 In the present population, the relationship between narcotic use and insomnia may be a reflection of pain impairing sleep quality. Insomnia in this population may also be adversely affected by concurrent anxiety, depression, polypharmacy, poor sleep habits, and substance abuse.

Many of the medications used among the present cohort can cause sleep fragmentation or alterations in normal sleep architecture or directly cause daytime somnolence. It is important to note that certain sedating agents may be contraindicated in patients with TBI and poor sleep quality. Larson and Zollman52 cautioned that benzodiazepines may lead to residual cognitive impairment after discontinuation, potentially by interfering with neural plasticity and recovery. A study by Rishi et al53 found that atypical antipsychotics (often used in the present population for anxiolysis and nighttime sedation) may increase the risk of more severe obstructive sleep apnea.

Failure to recognize sleep disorders in TBI may have an adverse impact on recovery. In a study of patients with TBI, Wilde et al28 found that those with concomitant sleep disturbances had worse performance on measures of cognition and verbal or visual delayed recall compared with those without sleep complaints. The authors concluded that TBI coupled with obstructive sleep apnea is associated with significant impairments of sustained attention and memory compared with patients with TBI alone.

The relationship between brain injury and sleep disorders is complex and poorly understood. Direct trauma and shearing forces can cause diffuse degeneration of the white matter, which may adversely affect axonal neurotransmission of substances integral in CNS regulation of the sleep-wake cycle.16 TBI may disrupt central regulation of sleep and wakefulness in several ways. Injury to the suprachiasmatic nuclei may disrupt pineal gland synthesis of melatonin.24 TBI resulting in hypothalamic-pituitary axis injuries may also result in decreased levels of wake-promoting neurotransmitters, such as hypocretin (orexin-A) and histamine, leading to hypersomnia,54,55 and cerebrospinal levels of hypocretin-1 have been found to be depressed in patients with acute TBI.22 Relationships between type of brain injury and type of sleep disorders have not been described.

The present study has several limitations. As a retrospective study, it is subject to selection bias, and the impact of mechanism of injury on sleep disorders would be better studied in a prospective cohort. In addition, the study population comprised patients with combat-related injuries. Although the results may be of limited applicability to civilian patients with TBI, they highlight the long-term sequelae of TBI, which are applicable to noncombat-related injuries. The percentage of patients reporting excessive daytime somnolence was higher than the percentage of patients with an ESS score of ≥ 10, which may reflect both the limitations of the ESS56,57 and the somewhat arbitrary threshold of 10 as a cutoff for normal. As mentioned previously, the majority of the cohort was using psychoactive medications, and several patients had concomitant PTSD, which likely contributed to their sleep complaints. The high rate of polypharmacy precluded meaningful comparisons regarding medication use; however, this is likely similar to other TBI populations. Given that difficulties in initiating and maintaining sleep, sleep fragmentation, and poor sleep quality were nearly universally present, defining who had insomnia was challenging in this cohort. Finally, by nature of the cohort, several patients had chronic pain or underlying obstructive sleep apnea or were using medications that could contribute to sleep disruption. We used a more narrowed definition of insomnia to decrease the impact of confounding factors associated with sleep fragmentation. Although this narrowed definition likely led to underestimates of the prevalence of insomnia in this cohort, we believe that it makes our findings more clinically applicable. On average, the patients in this study were evaluated . 1 year after TBI, which should reflect long-term sequelae of TBI.

Most returning soldiers report poor sleep quality, and the impact of combat deployments on physical and psychologic health is complex.58 Diminished sleep quality is likely further accentuated in those with TBI. The prevalence of sleep disorders among military service members has increased dramatically over the past decade. Among service members, obstructive sleep apnea has increased from 3,563 cases diagnosed in 2000 to 20,435 in 2009, with a fourfold increase in those aged 20 to 24 years.59,60 Similarly, the diagnosis of insomnia has increased from 1,013 in 2000 to 19,631 in 2009.61

There is increasing recognition that sleep disruption can complicate TBI, and unrecognized or untreated sleep disorders can worsen outcomes, increase disability, or impair rehabilitation. Although sleep complaints are nearly universal among those sustaining TBI, it appears that the mechanism of injury may play a role in the development of specific sleep disorders. Given the extremely high prevalence of sleep complaints, patients with TBI should be evaluated for sleep disorders or referred for formal sleep evaluations because recognizing and treating these conditions may improve outcomes.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense, or the US Government.

All variables in Table 5 with P < .20 were entered into this model (age, excessive daytime sleepiness, fragmented sleep, poor sleep quality, PTSD, blast injury, blunt injury, narcotics). The variable fragmented sleep was excluded from this model because it was highly correlated with the variable poor sleep quality (Spearman correlation r ± 0.513). Blast injury was excluded from this model because it was highly correlated with blunt injury, which was to be expected because this is a dichotomous variable and every patient had one or the other type of injury. PTSD and on narcotics were excluded from this model after using backward, stepwise regression to assess model performance. See Table 1 legend for expansion of abbreviations.

All variables in Table 7 with P ≤ .20 were entered into this model (poor sleep quality, No. [psychoactive medication] classes, No. [psychoactive] medications, and on narcotics). The variables No. psychoactive classes and No. psychoactive medications were highly correlated, so only the No. psychoactive medications was incorporated into the final model.

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